S291: PHASE I/II STUDY OF RILZABRUTINIB, AN ORAL BRUTON TYROSINE KINASE INHIBITOR, IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA: LONG-TERM FOLLOW-UP
Authors: D. J. Kuter, M. Efraim, Z. Kaplan, J. Mayer, P. Choi, A. G. Jansen, V. McDonald, R. Baker, R. Bird, M. Garg, J. Gumulec, M. Kostal, T. Gernsheimer, W. Ghanima, M. Yao, A. Daak, N. Cooper
Journal: HemaSphere (2022)

Background: Immune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibody-mediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and high bleeding risk. In a global phase I/II trial (NCT03395210) of heavily pretreated patients with long-standing disease, the Bruton tyrosine kinase inhibitor rilzabrutinib showed a rapid and durable platelet count increase and was well tolerated. We present results for patients initiating rilzabrutinib 400 mg BID who are continuing in the long-term extension (LTE). Aims: Assess if the efficacy and safety of rilzabrutinib 400 mg BID continue to be maintained in LTE patients on rilzabrutinib ± concomitant medication. Methods: Patients with 2 baseline platelet counts <30×109/L were required to have responded to ≥1 prior ITP therapy but at baseline were unable to maintain an adequate response to prior/concomitant therapies. The main treatment period was 24 weeks; patients who achieved platelet counts ≥50×109/L at ≥50% of the visits during the last 8 weeks of the main period were permitted to continue 400 mg BID in the LTE. Primary endpoints were safety and efficacy (≥2 consecutive platelet counts ≥50×109/L and increased ≥20×109/L from baseline without requiring rescue medication). Stable doses of concomitant ITP medication (thrombopoietin-receptor agonists [TPO-RA] and corticosteroids [CS]) were allowed for patients with inadequate platelet response. Patients who received rescue medication discontinued from the study. All patients provided informed consent. Results: At baseline, the 45 patients initiating 400 mg BID in the main period had a median age of 49 years, median duration of ITP of 6.1 years, median platelet count of 15×109/L, and a median of 4 unique prior therapies (24% prior splenectomy). A total of 15 patients (33%) received rilzabrutinib monotherapy, and 30 had concomitant therapy (TPO-RA n=13 [29%], CS n=12 [27%], TPO-RA + CS n=5 [11%]). Primary platelet response was achieved by 18 patients (40%): 6 on monotherapy and 12 on concomitant medication. Platelet counts of ≥50×109/L, ≥30×109/L, and ≥20×109/L from baseline were maintained for a median of 71%, 95%, and 87% of weeks, respectively. As of 21Jan2022, 16/60 patients in the main study population had proceeded to LTE, of whom 11 were ongoing. Five LTE patients (31%) continued on rilzabrutinib monotherapy and 11 used concomitant medication (TPO-RA n=2 [13%], CS n=7 [44%], TPO-RA + CS n=2 [13%]; Figure); 1 patient used rescue medication. Median platelet count at LTE entry was 87×109/L. In patients on rilzabrutinib monotherapy, the median platelet count was 68×109/L, which was sustained at 6 months of follow-up (Table). In all LTE patients, platelet counts ≥50×109/L, ≥30×109/L, and ≥20×109/L from baseline were maintained for a median of 88%, 100%, and 97% of weeks, respectively. In patients on rilzabrutinib ± concomitant medication, results were consistent at 3 and 6 months of follow-up (Table). Three patients (19%) experienced related treatment-emergent adverse events (TEAEs), including 1 grade 2 upper respiratory tract infection. Three patients (19%) discontinued rilzabrutinib due to a TEAE. Six patients had ≥1 bleeding event, none were treatment-related; no related serious adverse events or deaths. The average ITP-BAT bleeding scale score at 6 months showed no increase in bleeding in the LTE. Image:Summary/Conclusion: With extended treatment duration, rilzabrutinib 400 mg BID showed durable clinical efficacy and was well tolerated in patients on rilzabrutinib ± concomitant medication.